{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T10:54:06Z","timestamp":1774436046611,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32002332"],"award-info":[{"award-number":["32002332"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Studies on pharmacokinetic drug\u2013drug interactions have highlighted the importance of P-glycoprotein (P-gp) because of its involvement in substrate drug transport. This study aimed to investigate the role of chicken xenobiotic receptor (CXR) in the regulation of P-gp and its influences on pharmacokinetics of P-gp substrate sulfadiazine. ALAS1 and CYP2C45, the prototypical target genes of CXR, were used as a positive indicator for CXR activation in this study. Results show that ABCB1 gene expression was upregulated, and transporter activity was increased when exposed to the CXR activator metyrapone. Using ectopic expression techniques and RNA interference to manipulate the cellular CXR status, we confirmed that ABCB1 gene regulation depends on CXR. In vivo experiments showed that metyrapone induced ABCB1 in the liver, kidney, duodenum, jejunum and ileum of chickens. In addition, metyrapone significantly changed the pharmacokinetic behavior of orally administered sulfadiazine, with a Cmax (8.01 vs. 9.61 \u03bcg\/mL, p &lt; 0.05) and AUC0-t (31.46 vs. 45.59 h\u00b7mg\/L, p &lt; 0.01), as well as a higher T1\/2\u03bb (2.42 vs.1.67 h, p &lt; 0.05), Cl\/F (0.62 vs. 0.43 L\/h\/kg, p &lt; 0.01) and Vz\/F (2.16 vs.1.03 L\/kg, p &lt; 0.01). Together, our data suggest that CXR is involved in the regulation of P-gp, and, consequently, the CXR activator can affect, at least in part, the pharmacokinetic behavior of orally administered sulfadiazine.<\/jats:p>","DOI":"10.3390\/antibiotics11081005","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T22:03:42Z","timestamp":1658873022000},"page":"1005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potential Pharmacokinetic Effect of Chicken Xenobiotic Receptor Activator on Sulfadiazine: Involvement of P-glycoprotein Induction"],"prefix":"10.3390","volume":"11","author":[{"given":"Mei","family":"Li","sequence":"first","affiliation":[{"name":"School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyong","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, School of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9534-1083","authenticated-orcid":false,"given":"Yujuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-981-13-7647-4_2","article-title":"Abc Family Transporters","volume":"Volume 1141","author":"Liu","year":"2019","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.drudis.2021.09.020","article-title":"Advances in Understanding the Role of P-Gp in Doxorubicin Resistance: Molecular Pathways, Therapeutic Strategies, and Prospects","volume":"27","author":"Mirzaei","year":"2022","journal-title":"Drug Discov. 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